Research J. Pharm. and Tech. 12(9): September 2019 ISSN 0974-3618 (Print) www.rjptonline.org 0974-360X (Online) RESEARCH ARTICLE Modern Possibilities of the Use of Non-Invasive Serological Biomarkers Severe in Population Studies Sergey Kotelevets1*, Sergey Chekh2, Zukhra Karakotova3 1North Caucasus State Academy, Medical Institute, PhD in Medical Sciences, Professor, Cherkessk, Russian Federation. 2North Caucasus State Academy of Humanities and Technology, Head of Department of Software Development, Cherkessk, Russian Federation. 3North Caucasus State Academy of Humanities and Technology, Medical Institute, PhD Student, Cherkessk, Russian Federation. *Corresponding Author E-mail: [email protected] ABSTRACT: The ethnic and the gender factors materially affect the prevalence of gastric atrophy. All the patients were divided into five ethnic groups: Russians, Karachays, Abazins, Circassians, Nogais. The decrease in serum gastrin-17 less than 10 pmol/l is a sensitive and specific biomarker for antral mucosal atrophy, pepsinogen-I less than 25 µg/l is a corpus mucosal atrophy biomarker (Se − 89% and 92%, Sp − 97% and 96%). Gastrin-17 and pepsinogen-I are also sensitive and specific biomarkers for mild, moderate, severe atrophy of the antrum and corpus (for severe antral mucosal atrophy Se − 96%, Sp − 92%, for severe corpus mucosal atrophy Se − 88%, Sp − 97%). A total of 75 patients with multifocal atrophic gastritis were examined histologically. 67 patients had gastrin-17 <10 pmol/l and pepsinogen-I <25 µg/l at the same time. 7 patients had gastrin-17 from 10 to 11.5 pmol/l, 1 patient had gastrin-17 = 19 pmol/l (Se − 89%). Therefore, the level of gastrin-17 and pepsinogen-I simultaneously decreases among patients with multifocal atrophic gastritis. The prevalence of atrophic gastritis is significantly different among some ethnic populations living in the same territory under the same environmental and living conditions. These differences prove the presence of genetic polymorphism in different ethnic groups of the population. KEYWORDS: Atrophic Gastritis, Serological Screening, Gastrin-17, Pepsinogen-I, Population. INTRODUCTION: They were more frequent among Europeans compared to Background: Evenks and Khakas, while their prevalence was record The ethnic factors materially affect the prevalence of high among Tuvans2. The incidence was higher among gastric atrophy. As an example, it is significantly urban residents of Siberia compared to European different between Caucasians and Mongoloids. The countries and the United States. Among Yakuts, being differences were also found among Caucasians and representatives of a Mongoloid ethnic group, the ethnic Japanese; with a higher atrophy prevalence prevalence of atrophy is higher than among residents of among the Japanese1. Atrophy prevailed in Caucasians Eastern and Asian countries3. This pattern (with the when compared to Khakas and Evenks. Tuvans were as prevalence of atrophic lesions among residents of Japan, much affected by this pathology as non-native residents. Singapore, and China being higher than that among The prevalence of malignant diseases of the stomach Europeans) is very typical. It is influenced by their also differed between different ethnic groups. lifestyle and nutrition. Villagers in Yakutia lack fresh vegetables and fruits4,5,6,7, while fast food and refined products prevail in the diet of urban dwellers8. The Received on 28.05.2019 Modified on 03.07.2019 prevalence of gastric atrophy makes 16.7% among Accepted on 31.07.2019 © RJPT All right reserved Research J. Pharm. and Tech 2019; 12(9):4274-4282. Yakutsk residents and reaches 25.6% among the rural DOI: 10.5958/0974-360X.2019.00735.2 population3. The rate of atrophic changes of the stomach 4274 Research J. Pharm. and Tech. 12(9): September 2019 among residents of Novosibirsk is 2.5 times the rate Republic. 2031 of them were also examined for among rural residents9,10. PGI above 130 ng/ml is more antibodies to Helicobacter pylori. The urban population typical of Caucasians (29.9–32.1% of the population) was selected with the purpose of excluding as much as compared to Mongoloids (4.4–16.7%). Some studies did possible the impact of environmental and living not reveal any difference in the pepsinogen level conditions factors in various ethnic cohorts. Thus, we between Europeans and Asians11. managed to form ethnic cohorts with a high quality of randomization. The people were subjected to a non- The normal values of serum pepsinogen: invasive diagnostic examination after a previous clinical The normal values of serum pepsinogen were calculated examination according to the following selection for the population of West Siberia who did not have any criteria: aged 40 or older, signed informed consent for pathological stomach changes as follows: PGI − 30–130 clinical intervention. All the examined patients were µg/l, PGII – 4–22 µg/l. Normally, the PGI/PGII ratio divided into 5 ethnic groups: Russians, Karachays, should be more than three12,13. Pepsinogen-I reduction Abazins, Circassians, and Nogais. The enzyme below 25 µg/l is an evidence of atrophy, while the ratio immunodetection of markers in all 2713 patients was reduction below three confirms this fact11,14. In the conducted by antibody screening with a GastroPanel® Arkhangelsk Krai, PGI equaled to 100.2±5.3 ng/ml line diagnostic set (Finland Biohit Plc, Helsinki) and among surveyed patients aged 25−64. The scatter of included the detection of postprandial gastrin-17, fasting results is: 0.25–314.10 ng/ml6,15,16. pepsinogen-I, and anti-HP IgG. The mild, moderate, and severe atrophy of the antrum and stomach body mucosa Dependences between stomach atrophy and family were detected using the criteria developed by S.M. relationship: Kotelevets and S.A. Chekh19 (Table 1). Among randomly selected persons within the population studies, severe stomach atrophy was observed in 10.9% Table 1: gastritis Border marker of a certain degree of atrophy of of cases, while this value equaled to 27.6% among the mucous membrane of the stomach at atrophic gastritis of the antrum and body of the stomach people who had a family relationship. In case of Grade Atrophy Postprandial gastrin- pepsinogen-I stomach atrophy localized in the body of the stomach, severity 17 the prevalence was accordingly 12.6% and 48.3%11. The 1 No atrophy >10 pmol/l >25 µg/l prevalence of atrophic gastritis within a population 2 Mild 7-10 pmol/l 15-25 µg/l group can be affected by genetic polymorphism17. 3 Moderate 4-7 pmol/l 9-15 µg/l 4 Severe 0-4 pmol/l 0-9 µg/l Gastric cancer risk correlates with the severity and extent of atrophic gastritis. Besides, Kyoto Global The atrophic gastritis stages were determined using the Consensus Report on Helicobacter Pylori Gastritis OLGA classification (Table 2). acknowledged as proven the statement that serum biomarkers of stomach atrophy are useful for the risk Table 2: Atrophic gastritis stages according to the OLGA 18 stratification . Thus, the diagnostics of atrophic gastritis classification as a precursory syndrome of gastric cancer with serum Stomach body markers is a modern non-invasive and patient-friendly Antrum Atrophy 0 none 1 2 3 method. weak moderate severe 0 none Stage Stage I Stage II Stage 0 III MATERIALS AND METHODS: 1 weak Stage I Stage I Stage II Stage Classification of examined persons into ethnic III groups: 2 Stage Stage Stage III Stage moderate II II IV We examined 2713 persons for markers of antrum and 3 severe Stage Stage Stage IV Stage stomach body mucosa atrophy within the framework of III III IV the targeted republican program for early detection of patients with atrophic gastritis during 2012 and 2013 in Gastric cancer was detected by the method of P. Cherkessk, the capital of the Karachayevo-Cherkessian Sipponen according to Table 332. Table 3: Stomach risk calculation based on the severity of atrophy depending on its location in the antrum or body of the stomach. Sipponen et al. Int J Cancer. 1985. Stomach part Normal Non-atrophic Mild atrophy Moderate atrophy Severe atrophy stomach body gastritis Normal antrum 1 1 1 2 5 Non-atrophic antrum gastritis 1 2 2 2 5 Mild atrophic antrum gastritis 2 2 2 3 5 Moderate atrophic antrum gastritis 2 2 4 5 10 Severe atrophic antrum gastritis 18 18 36 36 90 4275 Research J. Pharm. and Tech. 12(9): September 2019 RESULTS: infection prevalence between different groups is equal. Prevalence of atrophic gastritis with mild, moderate, This fact confirms the equal everyday life conditions for and severe atrophy in both parts of the stomach all groups. Total number of patients was 2031, and 1582 among different ethnic groups: of them were HP-positive (78%). We defined the shares of AG patients with correspondent atrophy in persons of both sexes among The prevalence of Helicobacter pylori infection among the main ethnic groups residing in Cherkessk of the men and women, accordingly, is as follows: Abazins − Karachayevo-Cherkessian Republic of the Russian 84% and 80%; Circassians − 74% and 77%; Karachays Federation. The patients were defined by serum 76% of both men and women; Russians — 79% each. indicators: the criterion of mild, moderate, or severe No statistically significant difference was defined antrum atrophy was gastrin-17 whose level in such between these groups (p>0.05). As a result, it may be subjects was below 10 pmol/l and/or pepsinogen-I stated that there was no difference in the prevalence of reflecting mild, moderate, or severe stomach body Helicobacter pylori infection between the male and atrophy was below 25 µg/l. The prevalence was as female groups of the Abazin, Circassian, Karachay, and follows: Russians − 54% (1541 patients; 836 of them Russian ethnic groups. At the same time, a statistically have AG), Karachays − 53% (297/564 patient have AG), significant difference was observed between the Nogai Abazins − 59% (123/208 patients have AG), Circassians men and women – 91% and 59% (p<0.01).